PLGA-PEG-Maleimide from PolySciTech used in development of nanoparticles for treating CNS-associated tuberculosis.

 

Tuberculosis is a bacterial disease which most commonly infects the lungs however it can spread to other parts of the body. This disease is treatable in most parts of the body using antibiotic agents however is difficult to treat in the brain due to the blood-brain-barrier. Recently, researchers at Universidade Federal do Rio de Janeiro, Oswaldo Cruz Foundation, (Brazil), Universidade do Porto (Portugal) used PLGA-PEG-Mal (AI110) from PolySciTech (www.polyscitech.com) to create labeled nanoparticles for treatment of tuberculosis across the blood-brain-barrier. This research holds promise to improve therapeutic options for this lethal disease. Read more: de Castro, Renata Ribeiro, Flavia Almada do Carmo, Cláudia Martins, Alice Simon, Valeria Pereira de Sousa, Carlos Rangel Rodrigues, Lucio Mendes Cabral, and Bruno Sarmento. "Clofazimine functionalized polymeric nanoparticles for brain delivery in the tuberculosis treatment." International Journal of Pharmaceutics 602 (2021): 120655. https://www.sciencedirect.com/science/article/pii/S0378517321004609

“Highlights Clofazimine-loaded PLGA-PEG nanoparticles (NP-CFZ) were produced by nanoprecipitation. NP-CFZ were functionalized with a peptide (NP-CFZ-Pep) that binds transferrin receptor. NP-CFZ-Pep reduced drug toxicity and enhanced drug permeability across hCMEC/D3 cell. NP-CFZ-Pep can be administered by intravenous route and drive the drug to the brain. The NP-CFZ-Pep is promising to central nervous system tuberculosis treatment. Central nervous system tuberculosis (CNS-TB) is the most severe form of the disease especially due to the inability of therapeutics to cross the blood–brain barrier (BBB). Clofazimine (CFZ) stands out for presenting high in vitro activity against multi-drug resistant strains of Mycobacterium tuberculosis, however, CFZ physicochemical and pharmacokinetics properties limit drug penetration into the CNS and, consequently, its clinical use. The aim of this work was to develop polymeric nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) loaded with CFZ and functionalized with a transferrin receptor (TfR)-binding peptide, aiming brain drug delivery for CNS-TB treatment by the intravenous route. The poor water solubility and high lipophilicity of CFZ was overcome through its entrapment into PLGA-PEG NPs manufactured by both conventional and microfluidic techniques using the nanoprecipitation principle. In vitro studies in brain endothelial hCMEC/D3 cells demonstrated that CFZ incorporation into the NPs was advantageous to reduce drug cytotoxicity. The TfR-binding peptide-functionalized NPs showed superior cell interaction and higher CFZ permeability across hCMEC/D3 cell monolayers compared to the non-functionalized NP control, thus indicating the efficacy of the functionalization strategy on providing CFZ transport through the BBB in vitro. The functionalized NPs demonstrate suitability for CFZ biological administration, suggested with low plasma protein binding, off-target biodistribution and precise delivery of CFZ towards the brain parenchyma. Keywords: Brain delivery Clofazimine Targeted nanoparticles Transferrin-receptor Tuberculosis treatment”